ArticleJournal of cellular and molecular medicine
Liver fibrogenesis due to cholestasis is associated with increased Smad7 expression and Smad3 signaling.
Article in Journal of cellular and molecular medicine. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Anti-endoglin monoclonal antibody TRC105 prevents the increase of liver inflammatory biomarkers in a mouse model of cholestasis.Cellular and molecular life sciences : CMLS · 2026Article
- The central role of IL-6 in the differential effects of GLP-1 receptor agonists and metformin across multiple health conditions.Frontiers in immunology · 2026Review
- Long non-coding RNA GAS5 contributes to the progression of nonalcoholic fatty liver disease by targeting the microRNA-29a-3p/NOTCH2 axis.Bioengineered · 2022Article
- Interleukin-26 promotes the proliferation and activation of hepatic stellate cells to exacerbate liver fibrosis by the TGF-β1/Smad2 signaling pathway.International journal of clinical and experimental pathology · 2019Article
- Bone marrow derived-mesenchymal stem cells downregulate IL17A dependent IL6/STAT3 signaling pathway in CCl4-induced rat liver fibrosis.PloS one · 2018Article
- Longitudinal in vivo bioimaging of hepatocyte transcription factor activity following cholestatic liver injury in mice.Scientific reports · 2017Article
- Effect of Exogenous Fetuin-A on TGF-BioMed research international · 2016Article
- A synthetic TLR3 ligand mitigates profibrotic fibroblast responses by inducing autocrine IFN signaling.Journal of immunology (Baltimore, Md. : 1950) · 2013Article
- Ingredients of Huangqi decoction slow biliary fibrosis progression by inhibiting the activation of the transforming growth factor-beta signaling pathway.BMC complementary and alternative medicine · 2012Article
- TGF-β in progression of liver disease.Cell and tissue research · 2012Review
- Liver fibrosis secondary to bile duct injury: correlation of Smad7 with TGF-beta and extracellular matrix proteins.BMC gastroenterology · 2009Article
- Hyperoxia-induced neonatal rat lung injury involves activation of TGF-{beta} and Wnt signaling and is protected by rosiglitazone.American journal of physiology. Lung cellular and molecular physiology · 2009Article
- [Thoracic outlet syndrome: differential diagnosis and surgical therapeutic options].Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen · 2009Article
- Disruption of the Smad7 gene enhances CCI4-dependent liver damage and fibrogenesis in mice.Journal of cellular and molecular medicine · 2008Article
- Divergent transforming growth factor-beta signaling in hepatic stellate cells after liver injury: functional effects on ECE-1 regulation.The American journal of pathology · 2008Article
- [Economic aspects of surgical wound therapies].Der Chirurg; Zeitschrift fur alle Gebiete der operativen Medizen · 2008Article
- 50 years experience with Dupuytren's contracture in the Erlangen University Hospital--a retrospective analysis of 2919 operated hands from 1956 to 2006.BMC musculoskeletal disorders · 2007Article
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND/
aimsProfibrogenic TGF-beta signaling in hepatic stellate cells is modulated during transdifferentiation. Strategies to abrogate TGF-beta effects provide promising antifibrotic results, however, in vivo data regarding Smad activation during fibrogenesis are scarce.
methodsHere, liver fibrosis was assessed subsequent to bile duct ligation by determining liver enzymes in serum and collagen deposition in liver tissue. Activated hepatic stellate cells were identified by immunohistochemistry and immunoblots for alpha smooth muscle actin. Cellular localization of Smad3 and Smad7 proteins was demonstrated by immunohistochemistry. RTPCR for Smad4 and Smad7 was conducted with total RNA and Northern blot analysis for Smad7 with mRNA. Whole liver lysates were prepared to detect Smad2/3/4 and phospho- Smad2/3 by Western blotting.
resultsCholestasis induces TGF-beta signaling via Smad3 in vivo, whereas Smad2 phosphorylation was only marginally increased. Smad4 expression levels were unchanged. Smad7 expression was continuously increasing with duration of cholestasis. Hepatocytes of fibrotic lesions exhibited nuclear staining Smad3. In contrast to this, Smad7 expression was localized to activated hepatic stellate cells.
conclusionsHepatocytes of damaged liver tissue display increased TGF-beta signaling via Smad3. Further, negative feedback regulation of TGF-beta signaling by increased Smad7 expression in activated hepatic stellate cells occurs, however does not interfere with fibrogenesis.
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